ABSTRACT
Objective:To investigate whether salidroside (SAL) improves lung tissue injury in rats with severe pneumonia (SP) through mediating toll-like receptor 4/nuclear transcription factor-κB/NOD-like receptor protein 3 (TLR4/NF-κB/NLRP3) signaling pathway.Methods:Seventy-five Wistar rats were used in this study. Fifteen of them were randomly selected as the sham operation group, and the others were induced by endotracheal infusion of Klebsiella pneumoniae ( Kp) suspension to construct a rat model of SP. After modeling, the rats were randomly divided into four groups with 15 rats in each group: model group, low-dose SAL group (30 mg/kg), high-dose SAL group (60 mg/kg) and dexamethasone (DXMS, 15 mg/kg) group. The sham operation group and the model group were given the same amount of normal saline for seven consecutive days. The wet-dry weight ratio (W/D) of lung tissues in each group was detected. HE and TUNEL staining methods were used to observe the morphology of lung tissues and cell apoptosis. The levels of TNF-α, IL-1β, IL-6, IL-18 and IL-10 in bronchoalveolar lavage fluid (BALF) were detected by ELISA. The expression of TLR4, myeloid differentiation factor (MyD88), NF-κBp65, phosphorylated NF-κBp65 (p-NF-κBp65) and NLRP3 at protein level in lung tissues was detected by Western blot. Results:The rat model of SP was successfully constructed by endotracheal infusion of Kp suspension. Compared with the sham operation group, the model group showed more severe edema of lung tissues, increased W/D value ( P<0.05), loose and incomplete alveolar structure, edema of alveolar wall and thickened alveolar wall, massive inflammatory cell infiltration, increased apoptosis rate as well as higher levels of TNF-α, IL-1β, IL-6 and IL-18 and lower lover of IL-10 in BALF. Moreover, the relative expression of TLR4, MyD88, NF-κBp65, p-NF-κBp65 and NLRP3 at protein level in lung tissues was increased in the model group ( P<0.05). Gradually improved pathological injury of lung tissues, decreased W/D value ( P<0.05), recovered alveolar structure, reduced alveolar wall edema and decreased cell apoptosis rate were observed in the low-dose and high-dose SAL groups as well as the DXMS group as compared with those of the model group. Besides, the three groups also showed decreased levels of TNF-α, IL-1β, IL-6 and IL-18 and increased level of IL-10 in BALF, and inhibited expression of TLR4, MyD88, NF-κBp65, p-NF-κBp65 and NLRP3 at protein level in lung tissues ( P<0.05). DXMS performed better in improving lung injury in rats with SP, followed by high and low doses of SAL ( P<0.05). Conclusions:SAL could reduce cell apoptosis and improve the Kp-induced lung injury in rats. The mechanism might be related to the blockage of TLR4/NF-κB/NLRP3 signaling pathway activation and inhibition of inflammatory factor expression.
ABSTRACT
BACKGROUND:Flexible intramedulary nailing and external fixation for pediatric femoral shaft fractures are two common methods in the clinic. It remains controversial which fixation methods are better. OBJECTIVE:To systematicaly evaluate the therapeutic effects of flexible intramedulary nailing and external fixation for pediatric femoral shaft fractures. METHODS: A computer-based search was performed on PubMed, Embase, Medline, and Cochrane library for literatures on clinical controled trials of flexible intramedulary nailing and external fixation for pediatric femoral shaft fractures published before November 25, 2014. Literature language was not limited. The age of subjects was from 3 to 15 years. Modified Jadad was utilized to assess methodological quality of the included studies. Meta-analysis was carried out using Stata 12.0 software. RESULTS AND CONCLUSION:Six papers involving 237 patients were included. Meta-analysis results showed that compared with external fixation, a low incidence of overal complications [relative risk (RR)=0.30, 95% confidence interval (CI): 0.19-0.46;P < 0.001] and pin-hole infection (RR=0.286, 95%CI: 0.13-0.61;P= 0.001), but a high risk of needle tail irritation (RR=1.86, 95%CI: 1.35-2.56;P < 0.001) were found folowing flexible intramedulary nailing. No significant differences in other complications were found between the two groups. These results confirm that compared with external fixation, elastic intramedulary nail has fewer complications and faster fracture healing. Elastic intramedulary nail is recommended for single pediatric femoral shaft fractures. However, external fixation is a better option for high energy injury of lower limbs, multiple trauma or severely soft tissue injury.
ABSTRACT
Autophagy is a metabolic pathway that widely presents in eukaryotic cells through the lysosomal mechanism to degrade its components. Autophagy regulates cell death not only by activating classic autophagosomal-lysosomal pathway, but also by influencing the occurrence and development of apoptosis and necrosis. Currently, the effect of autophagy in neuronal injury after acute cerebral ischemia/hypoxia and its specific mechanisms remain unclear. Studies have demonstrated that the autophagy after ischemia/hypoxia has a neuroprotective effect, such as maintaining neuronal homeostasis and reducing neuronal death; but other studies have also suggested that autophagy may aggravate neuronal injury after ischemia/hypoxia by activating multiple pathways, and even induce neuronal death.